Moreover, TNF-ɑ along with exogenous (i.e., bacterial products, cytomegalovirus) and endogenous ligands (i.e., nucleic acids in necrotic debris, hyaluronan and fibronectin fragments) of TLR3 and TLR4 were able to heighten the IL-22 effects in the joint microenvironment of RA patients [42] (Table 1). This evidence concerns the gene IL22 and rheumatoid arthritis.